Cerebral aneurysm rupture is a leading cause of hemorrhagic strokes. Because cerebral aneurysms are being more frequently diagnosed before they rupture and the prognosis of subarachnoid hemorrhage is still poor, treating clinicians are often required to judge which aneurysms are prone to progression and rupture. Unfortunately our understanding of the natural history of cerebral aneurysms is limited because the processes of aneurysm initiation, growth and rupture are not well understood. In this project we will focus on the initiation process. Despite general consensus that hemodynamic stress plays a fundamental role in the formation of cerebral aneurysms, there is no agreement about which hemodynamic variables are implicated in the underlying mechanisms responsible for aneurysm formation and development. We propose to conduct an exploratory study of the association between the local hemodynamic environment and the initiation site of intracranial aneurysms, with the goal of gaining a deeper insight into the mechanisms of pathogenesis and to identify hemodynamic indices able to localize the sites likely to develop aneurysms. To carry on these investigations we will use image-based computational fluid dynamics (CFD) modeling to represent the in vivo hemodynamics before aneurysm formation. The research will be organized around the following specific aims: 1) select 40 saccular aneurysm geometries with two different morphologies (terminal/bifurcation and lateral/sidewall) and 40 healthy artery geometries matching the aneurysm locations, 2) delete aneurysms to approximate the geometry before aneurysm formation and run CFD simulations for all models under different flow conditions, 3) analyze hemodynamic variables at formation sites and test newly proposed hemodynamic indices as predictors of aneurysm formation sites. This project will not only shed light into the underlying mechanisms governing aneurysm initiation, but also will guide the development of clinical tools for the evaluation and treatment of cerebral aneurysms. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to identify hemodynamic conditions associated to the formation of cerebral aneurysms using patient-specific image-based computational fluid dynamics to model the in vivo hemodynamics prior to the aneurysm initiation. This project will not only help to better understand the pathogenesis but will also attempt to determine which artery sites are most likely to develop aneurysms. The results obtained on this project will have a large impact on the management of intracranial aneurysms by improving risk assessment and treatment.